New Ni(II), Pd(II) and Pt(II) complexes coordinated to azo pyrazolone ligand with a potent anti‐tumor activity: Synthesis, characterization, DFT and DNA cleavage studies

• Published in: Applied organometallic chemistry 2018-02, Vol.32 (2), p.n/a
• Main Authors: Bakr, Eman A., Al‐Hefnawy, Gad B., Awad, Mohamed K., Abd‐Elatty, Hossam H., Youssef, Mohamed S.
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antiinfectives and antibacterials; antimicrobial; Antimicrobial agents; antioxidant; Antioxidants; antitumor; azo‐pyrazolone dyes; Bacteria; Biological activity; Cancer; Chemistry; Cleavage; Coordination compounds; Deoxyribonucleic acid; DFT studies; DNA; DNA cleavage; Fungicides; Hydrogen peroxide; Infrared radiation; Ligands; Magnetic moments; metal complexes; Nickel; Palladium; Platinum; Pyrazolones; Thermal analysis; Three dimensional models
• ISSN: 0268-2605; 1099-0739
• DOI: 10.1002/aoc.4104

The absolute necessity to fight some class of tumor is perceived as serious health concerns, so the discovery and development of effective anticancer agents are urgently needed. (E)‐4‐((2‐hydroxyphenyl)diazenyl)‐3‐phenyl‐1H‐pyrazol‐5(4H)‐one, HL, and its Ni(II), Pd(II) and Pt(II) complexes were synthesized and the biological activity was evaluated for antitumor, antioxidant and antimicrobial activity as well as DNA cleavage. Their structures were assigned depending on the elemental analysis, conductivity, magnetic moment, spectral measurements (IR, 1HNMR, mass and UV–Vis) and thermal analysis. 3D molecular modeling using DFT method confirmed that the geometrical structures agree well with the suggested experimental ones. The antitumor activity was evaluated against four different cell lines using MTT assay. The ligand HL showed a potent cytotoxic activity compared to 5‐fluorouracil as a reference drug. For metal complexes, the order of activity was: Pd(II) > Ni(II) > Pt(II). A remarkable antioxidant activity for the ligand HL was recorded. It was higher than that of the metal complexes. Results of antimicrobial experiments revealed that all compounds were moderate to highly active against selected bacterial strains but inactive as antifungal except Pd(II) which showed a moderate antifungal activity. Gel electrophoresis showed insignificant nucleases activity for the ligand or its metal complexes even in the presence of H2O2 providing protection of DNA from damage. The antitumor activity of our compounds may be not due to DNA cleavage but may be referred to a mechanism similar to that of 5‐fluorouracil which interfere with DNA replication. The present work suggests the use of this ligand in the design and development of new anticancer drugs. An aryl azo pyrazolone ligand HL, and its Ni(II), Pd(II) and Pt(II) complexes were synthesized, characterized and biologically screened as antitumor, antioxidant and antimicrobial agents. 3D molecular modeling using DFT method confirmed that the geometrical structures agree well with the suggested experimental ones. The ligand HL showed a potent cytotoxic activity higher than the metal complexes. Gel electrophoresis showed insignificant nucleases activity for the ligand or its metal complexes even in presence of H2O2 providing protection of DNA from damage.